Orthopaedic surgeons and the medical device industry: The threat to scientific integrity and the public trust

Transcription

1 Washington University School of Meicine Digital Open Access Publications Orthopaeic surgeons an the meical evice inustry: The threat to scientific integrity an the public trust Richar H. Gelberman Washington University School of Meicine in St. Louis Davi Samson Wolff an Samson PC Sohail K. Mirza Dartmouth-Hitchcock Meical Center John J. Callaghan University of Iowa Health Care Vincent D. Pellegrini University of Marylan School of Meicine Follow this an aitional works at: Part of the Meicine an Health Sciences Commons Recommene Citation Gelberman, Richar H.; Samson, Davi; Mirza, Sohail K.; Callaghan, John J.; an Pellegrini, Vincent D.,,"Orthopaeic surgeons an the meical evice inustry: The threat to scientific integrity an the public trust." The Journal of Bone an Joint Surgery.92, (2010). This Open Access Publication is brought to you for free an open access by Digital It has been accepte for inclusion in Open Access Publications by an authorize aministrator of Digital For more information, please contact

2 765 COPYRIGHT Ó 2010 BY THE JOURNAL OF BONE AND JOINT SURGERY, INCORPORATED the Orthopaeic forum An AOA Symposium Orthopaeic Surgeons an the Meical Device Inustry The Threat to Scientific Integrity an the Public Trust By Richar H. Gelberman, MD, Davi Samson, Esq, Sohail K. Mirza, MD, MPH, John J. Callaghan, MD, an Vincent D. Pellegrini Jr., MD The purpose of this article is to relate recent actions by the Unite States Department of Justice, the Institute of Meicine, the Association of American Meical Colleges (AAMC), an others to the specific challenges confronting the specialty of orthopaeic surgery. Further, it strives to reconcile the uty an value propositions associate with the orthopaeic surgeon-meical evice company relationship, with the persistent risks that are attenant to that relationship, an to evelop a new path one that strives to restore the integrity of scientific investigation an ay-toay clinical ecision making, while proviing justification for future physician-inustry interaction. To consier the topic in perspective, it is interesting to assess the origins of the current moel of physicianinustry interaction as they relate specifically to the issues currently confronting the specialty of orthopaeic surgery. In 1980, novel legislation in the fiel of intellectual property, the Bayh- Dole Act, for the first time allowe universities an nonprofit organizations to replace the government as the principal beneficiaries of commercial evelopment resulting from basicscience an clinical research. In essence, the act transferre the ownership of iscoveries mae with the help of Disclosure: The authors i not receive any outsie funing or grants in support of their research for or preparation of this work. One or more of the authors, or a member of his or her immeiate family, receive, in any one year, payments or other benefits in excess of $10,000 or a commitment or agreement to provie such benefits from commercial entities (Meartis, Wright Meical, Lippincott Williams & Wilkins, University of Washington [royalties], an DePuy [consultation, intellectual property, an royalty agreement]). J Bone Joint Surg Am. 2010;92: oi: /jbjs.i.01164

3 766 feeral research grants to the universities an small businesses where those iscoveries were mae. On the face of it, the Bayh-Dole Act mae sense. Convince that government ownership ha eterre the evelopment of incentives necessary to promote innovation an ha severely inhibite prouctivity, supporters saw the act as a remey for the epresse American economy in the 1970s. The goal of the act was specific to aress the concern that American firms were not using acaemic research efficiently for commercialization an it intene to remey that shortcoming by facilitating patenting an licensing by U.S. universities of inventions from feerally fune research. If successful, it coul help to usher in a new era of innovation in America. It was an interesting concept one that supporters claim le to a very positive chain of events an to years of U.S. leaership in a variety of fiels. The pharmaceutical an meical evice inustries le the way, ramatically increasing licenses an patents in the years that followe the aoption of the legislation. For the meical profession, the result was, accoring to one observer, a moern alchemy, where... ivory towers were being turne into gol an society was benefiting from hunres of novel treatments introuce for ahostofiseases. 1 While that view may have been accurate for a time, a series of increasing concerns evelope over the years following passage of the Bayh-Dole Act. In what has been terme one of the most serious unintene consequences of a major piece of legislation, physician scientists an their universities evolve graually from noble, highly truste institutions into something closer to venture capital firms 1. The increase in substantial financial conflicts of interest between clinical investigators an inustry rose to such a remarkable level that, by 2007, a large percentage of physicians 2 an almost two-thirs of the epartment chairs in America 3,4 ha important personal relationships with inustry, serving as consultants, members of scientific avisory boars, an pai speakers. With regar to the integrity of ecision making, however, the resultant risks were slow to be appreciate. Only recently have acaemic meical centers an professional societies begun to aress, in a systematicway,thecoreissue the temptation of physicians to eviate from their professional obligations for economic or other personal gain 2,3,5,6. Graually, it became clear that the presence of self-interest associate with sponsore research substantially istorts how iniviuals make choices in the clinic, in the classroom, an in the laboratory. Very recently, leaers of some professional societies an acaemic meical centers havetakenonthechallengeofetermining how scientific objectivity canbemaintaineinthefaceof potentially compromising relationships ensuing from grants, royalties, anequityholingsprovietoiniviual investigators an to acaemic institutions Despite some early efforts at selfregulation, the complications associate with the inustry-physician partnership became so severe in the early 2000s that the Department of Justice entere criminal conspiracy complaints against five orthopaeic meical evice companies, alleging violations of the Feeral Anti-Kickback Statute. The government accuse the companies of using consulting agreements with orthopeic surgeons as inucements to use a particular company s artificial hip an knee reconstruction an replacement proucts. 15 Furthermore, the investigation reveale that it was common practice across America, from the late 1990s through 2006, for physicians, who performe work of little or no value, to be reware with consulting contracts, lavish trips an other perquisites 15.In aition, it foun that physician consultants faile to isclose the existence of their relationships to the centers where the surgeries were performe an to the patients who were uner their care. Compliance in the Wake of the Big Five Nonprosecution an Deferre Prosecution Agreements In 2007, Zimmer, DePuy Orthopaeics, Biomet, Smith an Nephew, an Stryker Orthopaeics (a ivision of Howmeica Osteonics) were ientifie by the U.S. Department of Justice as proviing improper financial incentives to orthopaeic surgeons to inuce their selection of hip an knee evices. To avoi criminal prosecution, these companies entere into nonprosecution an eferre prosecution agreements pursuant to which they agree to eighteen months of feeral monitoring to ensure their implementation of corporate compliance proceures. Because these companies together account for nearly 95% of the market for hip an knee surgical implants 16, this innovative prosecutorial arrangement sought to change the way an entire inustry i business. Allege violations of the Feeral Anti-Kickback Statute 17 were the basis of this unpreceente inustry-wie enforcement effort. The companies ha been accuse of proviing financial inucements to orthopaeic surgeons through consulting agreements an irect financial perquisites. At the crux of these allegations was the unerlying conflict of interest that the Anti-Kickback Statute is esigne to prevent: the conflictbetweenwhatisinthesurgeon s financial interest an what is in the best interest of the patient. The nonprosecution an eferre prosecution agreements have now ene, successfully marking a new era for the orthopaeic evice inustry. As the feeral monitor for Smith an Nephew, one of us (D.S.) personally observe the important compliance improvements an inustry transformation achieve by this process throughout 2007 to The strict compliance measures manate by the nonprosecution an eferre prosecution agreements in areas of (1) etermination of the nee for health-care professional consultants, (2) payments to health-care professional consultants, (3) isclosure an transparency

4 767 regaring financial arrangements with health-care professionals, an (4) compliance training an hotline reporting have all fostere an inustry-wie culture of improve compliance an accountability. Of course, whether the inustry will continue on this positive path remains to be seen, but the structural sea changes have occurre an corporate policies are in place to ensure continue success. Although the nonprosecution an eferre prosecution agreements process explicitly applie irectly to only the companies, the unacceptable transactions an relationships that were the subject of the feeral proceeing always involve two parties: a company an a professional. Now with the expiration of the nonprosecution an eferre prosecution agreements, the healthcare professional sie of the arrangement will continue to be aresse. It is certain that public scrutiny is far from over because, as state by Davi Rothman, PhD, professor at Columbia University an presient of Columbia University s Institute on Meicine as a Profession, the rules of the game have change. 18 The Department of Health an Human Services Office of Inspector General will expan enforcement efforts by targeting iniviual orthopaeic physicians who are as culpable as meical evice companies for entering into illegal arrangements 18, an these expane enforcement efforts will likely result in negative public perception as to the professional sie of the subject relationships. Now that evice manufacturers have been ientifie an their compliance practices have substantially improve, there is a new challenge to counter any negative public view an buil on the progress achieve within the past eighteen months. To o this, it is imperative that physicians aopt an follow the strictest policies an coes of ethics regaring their interactions with the inustry to avoi both actual an apparent conflicts of interest. Inappropriate interactions between physicians an the meical evice an pharmaceutical inustries have threatene scientific integrity an iminishe the public trust. While much progress has been achieve, in this environment of welcome scrutiny an awareness where a hotline report canresultinafullinvestigationor whistle-blower suit physicians must be increasingly sensitive to public perception an be proactive in their approach to compliance to avoi suspicion an to maintain the integrity of the profession an its relationship with patients an its work proucts. This requires aherence to the most stringent coes of ethics an conflict-ofinterest policies, particularly those that aim to avoi the appearance of impropriety by placing reasonable restraints on physician-inustry interactions. Throughout the eferre prosecution agreement process, a number of hotline reports concerning meical evice company interactions with healthcare professionals were receive. They range from allegations of nepotism to the proviing of a free boat, expensive meals, basketball tickets, an a ay of pheasant shooting. While it may be argue that these kins of activities are e minimis an coul not possibly result in any inucement to use a certain prouct, such an argument appears to be at os with current opinion. Several recent stuies have emonstrate that offerings such as free lunches, subsiize trips, an even small gifts may influence a surgeon s meical jugment 19. Physicians themselves have cite these stuies an have propose the aoption of much stricter limitations on interactions with the pharmaceutical an meical evice inustries. For instance, on April 2, 2009, a group of physicians issue a special communication in the Journal of the American Meical Association that, in part, avise meical associations to move towar a complete ban on inustry funing 20. The reasoning for this stringent an progressive proposal is that current policies are not aequately etaile to prevent real or apparent unue influence or bias an that lack of strong uniform controls threatens to unermine the reputation of the profession. The movement to aopt more stringent policies is in irect response to increasing public concern over physician conflicts of interest cause by inustry ties an is consistent with an overall tren to further regulate an control physician-inustry interactions. The AAMC has recommene strict conflict-of-interest policies that place limitations on faculty-inustry relationships 21. Institutions such as Johns Hopkins 22 an Partners HealthCare 23 (a system that consists of Harvaraffiliate facilities such as Massachusetts General Hospital an Brigham an Women s Hospital) have recently announce more stringent conflict-ofinterest policies that restrict physicianinustry ties. There have also been recent legislative initiatives such as a Massachusetts law requiring pharmaceutical an evice manufacturers to ahere to a strict marketing coe of conuct 24 ; the Massachusetts law also manates isclosure of information relate to pharmaceutical an evice manufacturers financial arrangements with health-care professionals, as oes a recently announce policy of the Stanfor University School of Meicine 25 an a recently propose feeral law 26. Stringent policies such as those suggeste in the Journal of the American Meical Association proposal an avance in other recent initiatives establish bright-line rules to avoi both actual an perceive conflicts of interest an, ultimately, allegations of illegality. Courts have wiely hel that, regarless of best intentions, if merely even one purpose of an arrangement is to inuce feeral health-care program referrals, the Anti-Kickback Statute is violate The etermination of intent or purpose is highly subjective; what is a kickback to one may not be a kickback to another. Without strict rules that seek to avoi appearances of impropriety, it is ifficult to consistently etermine the bounaries of acceptability in physicianinustry interactions, particularly in areas such as the provision of gifts,

5 768 entertainment, meals, an hospitality; the existence or extent of inucement to use a particular prouct will epen on the circumstances an iniviuals involve. To aress the inherent subjectivity regaring physician-inustry interactions an overcome the public stigma, physicians shoul aopt the approach taken in the Journal of the American Meical Association proposal an other recent initiatives to ahere to the strictest coes of ethics an conflictof-interest policies. The revise Ava- Me (Avance Meical Technology Association) Coe of Ethics on Interactions with Health Care Professionals 31 serves as a useful stanar that aims to avoi negative perceptions. For example, its recommenations inclue (1) placing a blanket prohibition on the provision of entertainment (incluing activities such as theater, sporting events, an hunting); (2) setting forth stricter limitations on the provision of meals in terms of purpose an setting or location; an (3) prohibiting gifts, other than the occasional provision of items that benefit patients or serve a genuine eucational function an except for meical textbooks or anatomical moels use for eucational purposes have a fair market value of less than $100; notably, unlike the previous AvaMe Coe, the revise Coe oes not permit any type of noneucational brane promotional item, even if such an item is of minimal value an relate to the health-care professional s work or for the benefit of patients (such as pens, notepas, an mugs). Physicians shoul strongly consier aopting even stricter policies, such as a complete prohibition on the acceptance of inustry gifts regarless of purpose or value. In aition, although it woul not appear to be prohibite uner the AvaMe Coe for a health-care professional to atten a baseball game with a sales representative if the health-care professional is paying his or her own way, it may be regare as inappropriate by others. To avoi any perception of impropriety, these kins of situations shoul be avoie. The orthopaeic evice inustry has mae consierable progress towar instilling a commitment to compliance; however, the public perception of the integrity of the profession is still at risk, an there is a long way to go to elevate the inustry s reputation. The Duty Proposition: How Financial Entanglements Can Blur the Distinction Between Trae an Profession Guie by the Department of Justice, inustry has mae progress over the past few years towar managing conflicts effectively. Many surgeons, on the other han, continue to efen a culture of entitlement an exception 32, a efense that is increasingly ineffective against a public perception of greey octors perpetuate by the lay press. Healines of major newspapers highlight financial payments from inustry to physicians, without a balance explanation of context 33. Public trust has been eroe further by healines linking profit motives to the provision of care. For instance, an article entitle An Operation to Ease Back Pain Bolsters the Bottom Line, Too states that in the absence of better ata, critics in the fiel point to a ifferent reason for the fusion operation s fast rise: money. 33 Another article quotes a patient who warne, When an orthopeist says you nee surgery an you are in terrible pain, you assume he is right.... Think long an har. 34 It has become increasingly clear that, in the context of financial conflicts, amage perception matters more than nuance reality. At its core, the clinical relationship of physician an patient is a reciprocal clinical fielity. 35 Patients share sensitive information with their octors, rely on avice provie, an comply with treatments recommene. In exchange, they expect univie loyalty from their physicians. In a vulnerable state of sickness, patients yearn to believe that their octors are caring professionals practitioners who maintain their patients well-being ahea of conflicting self-interest an the interest of any other party 35.Inan era when orthopaeic surgeons earn more by performing surgery than by treating patients nonoperatively, the choice of proviing avice to patients regaring surgery compare with the act of performing the proceure constitutes a funamental conflict. Yet, solutions that call for the separation of the ecision-making process from the surgery itself are not feasible A more appropriate outcome woul have physicians reengage in meicine as a profession, not as a trae a goal that is facilitate by istancing patientcare ecisions, as much as possible, from extraneous financial arrangements 39. Tainte Science Inustry funing in orthopaeics is strongly associate with favorable outcomes, even for the scientific gol stanar of ranomize clinical trials. Results are favorable to the implant manufacturer in 73% of inustrysponsore stuies compare with 44% of inepenent stuies 40 (os ratio, 3.3; 95% confience interval, 2.4 to 4.5) for spine implants; 93% an 37%, respectively, for hip implants; an 75% an 20% for knee implants 41.A pattern of results favorable to the stuy sponsor is also observe more generally in biomeical research. Structure reviews of publishe stuies have shown a results bias favoring the sponsor, with an os ratio of 8.0 (95% confience interval, 1.1 to 53.2) for stuies fune by rug manufacturers, 3.6 (95% confience interval, 2.6 to 4.9) for stuies fune by biomeical suppliers, an 5.3 (95% confience interval, 2.0 to 14.4) for stuies fune by for-profit organizations 42. True innovation eserves to be reware. The long process from concept to prototype, to investigational evice, to evice approval, an to the elivery of the evice to the marketplace epens on the personal rive an sacrifice of the inventor an the risk borne by the sponsor. Feeral granting

6 769 TABLE I Conflict of Interest Ethical or Professional Interest Recommening tests or proceures Recommening participation in a clinical trial Support for research Writing prescriptions for rugs Using a specific prouct Self-Interest Performing the same tests or proceures Being pai for referring patients to a clinical trial Further funing only if positive results Being courte by the company Receiving gifts or being pai by the company agencies an founations rarely support the process. Successful innovation eserves financial rewar limite by market valuation rather than arbitrary threshols. The problem is that true innovation is rare. A report by the National Institute for Healthcare Management Research an Eucational Founation analyze 1035 new rug applications approve by the U.S. Foo an Drug Aministration between 1989 an Of those rugs, 361 (35%) ha a new active ingreient, but 674 (65%) ha an active ingreient that was alreay markete; 558 (54%) offere the ingreient in a ifferent osage route of aministration or a combination with other rugs; an 116 (11%) ha the ientical prouct alreay available. The average price of a new version was twice the price of the oler version. Device innovation may be even more rare with proliferation of me too proucts flooing the market with each new evice approval. the outcome is inepenent of personal gain 45. The first myth is that conflicts of interest are avoiable. Conflicts of interest are unavoiable. There are inherent conflicts between professional values an self-interest. Routine activities such as recommening tests or proceures have a conflict of interest if the recommening physician is also performing the same tests an proceures (Table I). Recommening participation in a clinical trial is often associate with being pai for referring patients to the trial. Support for research can be contingent on further funing only if positive results are prouce. Writing prescriptions for rugsoftenleastoacourtshipbythe rug company. Using a specific prouct is often associate with receiving gifts or being pai by the company. These are intrinsic conflicts associate with meical practice. Unavoiable intrinsic conflicts inclue the esire to obtain noteworthy finings, the esire to publish in acaemic journals, the nee to increase the number of research publications, an the ambition to avance a national reputation 46.Faculty in acaemic centers often seek to avance their careers, vinicate intellectual biases, receive accolaes from peers, an win research prizes. There is also satisfaction in being the first to fulfill the promise of a new proceure. These are some of the intrinsic unavoiable conflicts associate with research. The secon false belief is that bias is a eliberate choice. Bias is not a eliberate choice. Deliberate misrepresentation of ata an finings is frau 47. Frau is rare, but self-serving bias is pervasive. It affects iniviuals in their evaluations of themselves. Iniviuals often overestimate their own contribution to joint tasks 48.The above-average effect, where more than half of the iniviuals rate themselves within the top 50%, has been ientifie in ethics iscussions, managerial aeptness, prouctivity, an health aministration. Success is often attribute to skill, an failure, to ba luck 48. Iniviuals manifest ifferent notions of fairness 49.Whenworking har is compare with working long hours, the iniviuals who work more generally believe they shoul earn more an those who work less believe they shoul be pai equally 45. The thir false belief is that the biasing effects of gifts can be controlle. In a stuy of physicians, 76% believe strongly that rug avertisements an sales personnel were minimally important in influencing their prescribing habits, yet 49% change their prescribing habits on the basis of rug promotions 50. This iscrepancy suggests either an unwillingness to amit in- Myths an False Beliefs Social science research has provie important principles relate to financial conflicts of interest. We are all subject to self-serving bias 44. When iniviuals have a stake in the outcome, they ten to weigh arguments ifferently than if Fig. 1 Base on ata presente in the stuy by Orlowski an Wateska 52.

7 770 fluence or a lack of awareness of influence. The biasing effect is also prominent among physicians who atten sponsore lectures. After attening gran rouns sponsore by a rug company, the meical resients prescribe the company s rug favorably, with an os ratio of 8.4 (95% confience interval, 2.1 to 38.9) 51. They also prescribe inappropriately, with an os ratio of 7.8 (95% confience interval, 1.6 to 45.5). There was no ifference in rug choice between those who remembere the sponsor an those who i not. Some physicians strongly believe that attening a sponsore symposium oes not influence them. Recent finings of the effects of pai attenance at a conference have inicate, however, that the prescription of rugs increase from eighty-one units in the twenty-two months preceing a conference to 272 units in the seventeen months following the conference 52. Stuy of another rug showe that prescriptions change from thirty-four units in the preceing twenty-two months to eighty-seven units in the subsequent seventeen months (Fig. 1). The fourth myth is that small gifts o not matter. Social science research has shown that what is consiere TABLE II Attitues of Patients an Physicians Towar Gifts* inappropriate epens on the iniviual s perspective. In one stuy, 85% of meical stuents believe that it was inappropriate for a public official to accept a $50 gift from a contractor; however, only 46% of the meical stuents believe it was inappropriate for one of them to accept a $50 gift from a rug firm 53. Nearly all (97%) of nurse practitioners thought it was inappropriate for a public official to accept a gift from a contractor, an most (64%) thought it was inappropriate for a meical stuent to accept a gift from a rug company. Only 30%, however, believe that it was inappropriate for a nurse practitioner to accept a $50 gift from a rug company 53. Physicians an patients have ifferent attitues towar gifts. Patients are more likely than physicians to consier gifts as inappropriate an influential. Even small gifts, such as trips, inners, pocket knives, lunches, mugs, rug samples, textbooks, pens, an vieos, are more often consiere inappropriate an influential by patients than by physicians (Table II) 54. The fifth false belief is that bias is recognizable. Bias is ifficult to recognize. In a survey of resient physicians, 61% state that inustry promotions an context i not influence their own prescribing, but only 16% believe that Inappropriate (%) Influential (%) Gift Patients Physicians Patients Physicians Trip Dinner Pocketknife Lunch Mug Drug sample Major textbook Pen Vieo Small textbook *Base on ata in the stuy by Gibbons et al. 54. other physicians were similarly unaffecte 55. Every meical resient who consiere lunches an pens inappropriate ha accepte these gifts 55. The ifference shows inconsistency in physician attitues of self compare with others. The sixth false belief is that eucation reuces bias. Social science research has shown that awareness an knowlege about the biasing effect of gifts o not lea to a reuction in the effects of gifts 44,56. Limits of Disclosure Disclosure, as a metho for managing conflicts, has limitations. An unerlying funamental problem, terme moral license, hols that, like confession, isclosure provies the surgeon investigator a feeling of absolution without cleansing the potentially tainte message 56. Disclosure creates the false impression that biase avice is fair play. Professional meical associations often pay lip service to isclosure through unenforce an ineffective policies; members participating in the meetings frequently treat it casually as an obligatory burensome step. Despite stanars of professionalism establishe by the American Acaemy of Orthopaeic Surgeons (AAOS), the program for the 2007 Annual Meeting isclose only 71.2% (245) of 344 payments reporte by the five arthroplasty implant manufacturers on their web sites. While the AAOS program isclosures i not inclue ollar amounts, inustry web sites provie more etaile information, inicating that forty-seven consultants were pai over $1 million ayear Christopher J. Christie Jr., when he was U.S. Attorney for the District of New Jersey, state frankly that the target woul be shifte from inustry squarely to the orthopaeic surgeon: I ve ealt with the supply issue, now I nee to eal with the eman issue. 63 Legal action an external policing of this sort inicates how we an how our professional associations may have faile to protect the health of the public an the integrity of the profession.

8 771 In a concept escribe as anchoring, iniviuals have ifficulty unlearning, ignoring, or suppressing the use of knowlege even if, subsequently, it becomes apparent that the ata are inaccurate 56. When evience on which beliefs are mae is iscreite, the beliefs o not revert to their original state. They show the persistent effects of the iscreite evience. This phenomenon has been escribe as the curse of knowlege or the failure of evientiary iscreitation. 56 The Association of American Meical Colleges Recommenations The AAMC publishe guielines to facilitate the evelopment of institutional policies relate to financial conflicts 64,65. The guielines offer principles for examining an reesigning relationships with inustry to conform to stanars of meical professionalism. A report, issue in February 2008, entitle Protecting Patients, Preserving Integrity, Avancing Health: Accelerating the Implementation of COI Policies in Human Subjects Research calle on all meical schools an major universities to evelop an implement conflict-of-interest policies within two years 66. While orthopaeic surgeons are require to work closely with the evice inustry for research an prouct innovation, inustrial sponsorship of research iffers from feeral funing in several important ways. The subject of research in feeral funing is typically funamental science, whereas the subject for inustry funing is prouctbase science. The application process for feeral funing is complex compare with, typically, a simple one to two-page proposal for many inustrial grants. The application review process is peer review for feeral funing an business review for inustry funing. The egree of ifficulty in obtaining funing is ifferent. Feeral funing is competitive, an inustry funing is typically noncompetitive. Response time to the funing application is prolonge in feeral grants compare with a rapi review an response in inustry support. The contact between the sponsor an researcher is rare in feeral support, whereas it is frequent in inustry support. The timing for accrual of research ata is not typically specifie in feeral funing, whereas it can be iscreetly specifie in inustry funing. Access to all research ata for all stuy sites is usually not restricteinfeeralfuning.typically,it is very restricte in inustry funing. The relationship between a sponsor an the stuy finings is isintereste for feeral funing, whereas the sponsor is typically investe in the research outcomes for inustry funing. Other factors inclue ifferences in protecte time for researchers an investigators, salary support for investigators, an the ability to use funing for acaemic promotion or acaemic reputation. Policies relate to research activities have typically not aresse common relationships between investigators an sponsors. Investigators frequently report irect payments from inustry, holing office in the company, or receiving gifts from sponsors. However, these types of activities are rarely aresse in institutional policies 64,65,67. Our professional associations must evelop methos of proviing clinical context for evice manufacturers while shieling iniviual patient-care ecisions from unue commercial influence. Options inclue the evelopment of scientific review processes for the istribution of inustry research an eucation funs, the creation of registries to measure en results of implante evices, an the provision of transparent taxation mechanisms to allow evice manufacturers to sponsor the evelopment of continuing eucation courses. International Committee of Meical Journal Eitors Recommenations The International Committee of Meical Journal Eitors (ICMJE) publishe uniform requirements for manuscripts submitte to biomeical journals 68. These requirements are aime to protect the integrity of the research process an TABLE III International Committee of Meical Journal Eitors Uniform Disclosure Requirements for Potential Conflicts of Interest* 1. Boar membership 2. Consultancy 3. Employment 4. Expert testimony 5. Gifts 6. Grants an/or grants pening 7. Honoraria 8. Payment for manuscript preparation 9. Patents (planne, pening, or issue) 10. Royalties 11. Payment for evelopment of eucational presentations incluing service on speakers bureaus 12. Stock an/or stock options 13. Travel an/or accommoation expenses covere or reimburse 14. Other (err on the sie of full isclosure) *Accoring to Drazen et al. 71, isclosure applies to financial an nonfinancial relationships involving the author, institution, spouse or partner, an chilren uner eighteen years of age. Any personal, professional, political, institutional, religious, or other associations that a reasonable reaer woul want to know in relation to the submitte work, incluing all sources of revenue an any entity that coul broaly be consiere relevant for the thirty-six months prior to submission of the work, an all relationships outsie the thirty-six-month winow that reaers may want to know an coul reasonably criticize an author for not isclosing. Public funing sources, such as the National Institutes of Health or the Meical Research Council, nee not be isclose. the investigators. They require that the investigators retain access to all trial ata, control all eitorial an publication ecisions, an fully isclose the role of the sponsor. ICMJE has avocate for a rebuttable presumption stanar by which an investigator is presume to be ineligible to conuct human subjects research in which he or she has a significant financial interest, unless that investigator is uniquely qualifie to o so,

9 772 Fig. 2 Develope from recommenations in the Institute of Meicine 2009 report 75. an even then, only uner carefully monitore conitions. 69 The ICMJE has also introuce uniform requirements for isclosure While ollar amounts are not require, sponsors are ientifie for fourteen explicit categories of financial support (Table III) 70-72,74. Institute of Meicine Recommenations The Institute of Meicine publishe an extensive report on conflicts of interest in meicine 75. The report provies etaile steps to isclose, manage, an monitor aherence to management of conflicts of interest (Fig. 2, Table IV). The Value Proposition Despite the shortcomings of the surgeonmeical evice inustry relationship note in recent years, the value of the partnership, insofar as patient outcomes are concerne, is uneniable. In the early ays of implant evelopment, the intellectual contribution provie by the orthopaeic surgeon was more easily efine. Homer Stryker of Kalamazoo, Michigan, foune his own company, John Charnley evelope his own hip arthroplasty implant an brought it to inustry for commercialization, an the Association for the Stuy of Internal Fixation (AO/ ASIF) evelope a series of implants that were license to the Straumann Institute (Walenburg, Switzerlan) an istribute uner the Synthes traemark. Initially, these implants were small in scope an were use by relatively few surgeons. Regulation of the commercial manufacture an istribution of the implants in the 1950s an 1960s was ruimentary. Few questione the value of the partnerships in elevating the quality of care of patients with musculoskeletal isorers 76. The maturation of the fiel over the last half century has presente both opportunities an, more recently, threats to the orthopaeic surgeoninustry partnership, especially with regar to orthopaeic implant esign an istribution an to the eucation of professionals 2, If it is accepte that the evelopment of novel evices is beneficial, the process by which an orthopaeic surgeon may contribute to esign an istribution requires explicit ocumentation. Intellectual Property an Patents The criterion for royalty justification has come uner question most recently with the Department of Justice investigation. It has been establishe that intellectual property must be transferre between the orthopaeic surgeon an the company in a esign project if a royalty payment is to be mae. Many

10 773 TABLE IV Recommenations by the Institute of Meicine* General policy 1. Aopt an implement conflict-of-interest policies 2. Strengthen isclosure policies 3. Stanarize isclosure content an formats 4. Create a national program for the reporting of company payments Meical research 5. Restrict participation of researchers with conflicts of interest in research with human participants Meical eucation 6. Reform relationships with inustry in meical eucation 7. Provie eucation on conflict of interest 8. Reform financing system for continuing meical eucation Meical practice 9. Reform financial relationships with inustry for community physicians 10. Reform inustry interactions with physicians Clinical practice guielines 11. Restrict inustry funing an conflicts in clinical practice guieline evelopment 12. Create incentives for reucing conflicts in clinical practice guieline evelopment Institutional conflict-of-interest policies 13. Create boar-level responsibility for institutional conflicts of interest 14. Revise Public Health Service regulations to require policies on institutional conflicts of interest Supporting organizations 15. Provie aitional incentives for institutions to aopt an implement policies 16. Develop research agena on conflict of interest *Summarize from the Institute of Meicine report entitle Conflict of Interest in Meical Research, Eucation, an Practice. 75 consier the ownership of patents as the only true intellectual property. In law, however, patents, copyrights, traemarks, know-how, an trae secrets are all consiere intellectual property. Moreover, one coul conten that the involvement of surgical practitioners is helpful to the marketing of a evice in that such involvement shoul ensure the teaching of appropriate inications. Only patents (consiere true inventions), copyrights, an traemarks are grante exclusive rights protecte by law. Know-how (the ability to execute specific tasks or to prouce specific proucts [reucing an invention to practice]), however, is essential to the commercial success of many patente inventions. Only surgeons who have analyze their results critically an have emonstrate an unerstaning of the process of the evelopment of ieas to prouct evelopment can a value to the process. This unerstaning cannot be thoroughly accomplishe without extensive publication on the general topic (but not necessarily on the same implant or on the evice being evelope). Surgeon volume as the sole contribution is not an appropriate criterion for esign team involvement. Licensing Intellectual property is often transferre or sol by its inventor through the process of licensing. In the typical license agreement, the inventor charges a royalty to the purchaser licensee for the right to utilize the inventor s intellectual property, which often inclues relate unprotecte know-how as well as protecte patents. The inventor often transfers the right for the licensee to pursue patents base on the inventor s know-how. Most licensees recognize that know-how is central to commercialization of an invention. The monitors of the companies involve in the Department of Justice investigation agree with this interpretation an evelope a fair value amount in terms of the percentage of prouct sales (royalty buren) that is appropriate for an orthopaeic implant. Documentation of Work Effort Another important feature of the value proposition that has been evelope with regar to the royalty an consulting partnership is ocumentation of time, effort, an level of personal contribution to a project. The attorney minset of billing for time spent on a project (which is now require in the surgeon-inustry partnership) compare with the meical professional minset of billing for a complete task, clinic visit, or operation no matter how much time is require can be culturally ifficult for a meical professional. Many physicians are concerne about the potential for overbilling, whether it is relate to time or to the potential to justify the time on the basis of overocumentation. The aage that if it was not ocumente, it was not one is becoming an important stanar for the orthopaeic surgeon who consults with inustry. This process, however, shoul be easier for the surgeon to accept, as the same practice is being applie in the clinical setting, especially in cases in which the government is subsiizing care through Meicare. Fair market value for consulting time is ictate by outsie sources, most recently the monitors in the case of the eferre prosecution an nonprosecution agreements of the Justice Department. Fining a New Path for Orthopaeic Surgeons an Inustry: Beyon Disclosure All iscussions of conflict of interest to ate have hastene to enumerate the

11 774 o nots in physician relationships with inustry 7,11,14. Short of acknowleging the nee to preserve a positive interaction between meicine an inustry, however, none have sought to efine the parameters that woul characterize such a relationship. Such shoul also be our task. In orer to establish the new parameters of a constructive relationship with inustry, one first acknowleges that a relationship is important, if not essential, but that the current iteration is flawe. The critical error lies in the too liberal assignment of value to casual, nonsubstantive interactions that surgeons have with evice manufacturers. More holes in an acetabular shell, a 5 increase in the screw angle of a volar istal raial plate, or an aitional crosslink between spinal ros o not necessarily constitute material prouct improvements worthy of compensation. Seconly, while some of the errors have been egregious, the emonization of any relationship with inustry overshoots the mark an may lea to consierable harm in the long run. Some have propose a zero financial interest tolerance for physicians in critical positions that relate to inustry an provie potential for personal gain 20,79,80. Elimination of iniviuals from important tasks an groups because they receive appropriate compensation for critical contributions hanicaps the process an risks compromise of the quality of the final prouct. The contributions of those with such conflicts shoul be preserve by effective management of the relationship rather than by complete ismissal of the iniviual. Further, it is incumbent on our profession to repair any perception of isrepute insofar as inustry relationships are concerne. Moifications in physician behavior are the requisite for a healthy physicianinustry relationship, frame by the nee to move beyon simple isclosure in protecting ourselves from the perils of conflicts of interest. In the wors of Davi Korn, MD, Disclosure is essential but not sufficient, in characterizing the relationship between meical professionals an inustry 81. Components of a Healthy Physician-Inustry Relationship The futuristic approach to the constructive an ethically acceptable surgeoninustry relationship is preicate on four funamental principles: 1. Complete Disclosure an Transparency of Conflicts As has been articulate by some, a etaile an complete isclosure of financial an other substantive relationships is the starting point 81. Specific ollar amounts receive from inustry for efforts relate, irectly or inirectly, to the matter at han are isclose 12,82,83. This is most effectively accomplishe on a web site in the public omain; inee, most of the pertinent companies an an increasing number of universities alreay have such a policy. Objective reporting, such as income note on U.S. Internal Revenue Service form 1099, shoul be the basis for such eclarations. An unwillingness to isclose such relationships in this manner constitutes a basis for exclusion from any relate position, task, or group. Moreover, surgical consent forms for an operation shoul isclose the existence of such surgeon-inustry relationships to patients prior to the operative proceure being performe; some institutions have alreay aopte such a policy an stanarize form. This provies a context within which every observer may juge the potential bias of each respective contributor when presenting at a meeting, publishing a paper, or participating in a group iscussion. 2. Realistic Assessment of Actual Value Ae The material value of a surgeoninnovator s contribution is assesse by some ispassionate thir party, a group comprising representative iniviuals from inustry as well as a meical peer group. It is anticipate that there will be far fewer substantive compensable contributions as a result of this process. Likewise, it is assume that this will be the cornerstone of a more creible, ethical, an consistent system of rewar for surgeon esigners. 3. Objective Thir-Party Determination of Fair Market Value As the term implies, market forces appropriately etermine fair compensation for intellectual property transfer an consulting activity subsequent to a etermination of real value ae. It is expecte that the royalty loa for a given project varies within some range epenent on the magnitue an impact of each contribution an the relative success of the prouct in the marketplace. Similarly, natural market forces, overseen an approve by an objective thir party, shoul govern hourly remuneration rates for consulting activities. This is contraste with the current state, where a preetermine hourly rate for consulting activities an fixe percent of royalty loa is set arbitrarily, inepenent of market forces, by regulators who themselves may be conflicte. 4. Removal of Linkage from Patient-Care Decision Making Any conflict of interest, be it real or perceive, erives from the association of personal gain of the iniviual physician with the selection of a prouct which the physician participates in or even irects on behalf of the patient. Disclosure is no longer thought to confer immunity to being influence 84. If the role of the physician in the evelopment process is to be preserve because he or she as value, it then stans to reason that the triangle connecting the physician, the patient, an the venor must be interrupte. The physician is either issociate from the patient or from inustry in this triangle; any role in evice selection on behalf of the patient or the potential for personal gain by the physician (through reciprocity with the venor) is eliminate. While at first blush the isconnection of the physician from the ecision-making process for any iniviual patient appears contrary to the altruistic role of the physician, many health-care systems in the Unite States have alreay compromise the surgeon s ability to choose on behalf of the patient (e.g., by limiting implants to those supplie by certain venors

12 775 chosen by the institution, most often base on favorable pricing consierations). Common practice currently preclues a royalty benefit to a esigning surgeon base on patients care for in the surgeon s home institution, but some woul claim a serious conflict persists if the surgeon s payment remains correlate with the use of any specific implant. An alternative hybri scenario might create a thir-partyaministere innovator pool that provies a reimbursement premium to surgeon-innovators whenever the proceure in question is performe, irrespective of which implant is use in any particular patient or which company manufacture it. Uner such a system, the surgeon-esigner is reware for participation in the prouct evelopment process in a manner not connecte with the use of any specific evice in any particular patient. For example, the preetermine royalty loa of a given evice from each manufacturer might be pai to an inepenently governe fun rather than to any iniviual esigning surgeon. The aggregate pool of royalty payments relate to surgeon-esigne evices woul then be istribute to participating surgeon innovators on the basis of relevant metrics such as the time spent on projects an the success of the evices, rather than having payment linke to the success of any specific implant with which the surgeon may be involve. This approach woul retain a more general incentive for the surgeon-innovator while separating the irect surgeon link to inustry; it therefore also potentially preserves the physician role as agent in ecision making for the iniviual patient. Likewise, the establishment of such a meical evice tax coul also perpetuate inustry sponsorship of research an eucation, consiering that the incentive for inustry to continue its support of such activities is iminishe by removal of its irect link to the surgeon who makes implant-purchasing ecisions. No matter how the surgeonesigner is remove from the conflict-ofinterest triangle (e.g., eliminating the prospect of financial gain as was the case in the early history of implant evelopment, or ivorcing the physicianinnovator from the process of evice selection for any iniviual patient), there will be at least a temporary perio when review of these situations by a ispassionate thir party (an ethicist) will a consierable value in reassuring the public that the meical profession has aopte an ethical an transparent approach to relationships with inustry. It is likely that there will be increasing eman for such iniviuals proviing counsel to acaemic health centers in the years to come. Beyon the role of avisor, a principal function of such an iniviual might be to provie a bining review an ajuication of conflict-of-interest isclosure as well as a etermination of the appropriate relationship structure between inustry anphysician-innovatorsaswemove forwar. Whatever approach is aopte to raise our profession from the present quagmire must ensure ethical relationships between inustry an the meical community an must restore the public trust in the treating physician as having the welfare of the patient as the principal motive. A thoughtful an reflective ialogue involving meicine, the lay public, an inustry is essential. Elements of such a relationship inclue complete an full isclosure, a realistic assessment of value ae, an inepenent etermination of fair market value, an elimination of any linkage of the surgeon to either specific patient ecision making or a relationship with inustry that provies for personal gain. Ami all of this, we strive to protect the ethical interaction between meicine an inustry that has fuele proper meical avances over the years. For all those who partake in the iscussion, nothing less than genuine altruism will be require, as well as a clear an irrevocable unerstaning that what is past has passe an the future of all relationships with inustry will look very ifferent. Our choice is simple; we can elect to be part of the solution or a continuing part of the problem. Richar H. Gelberman, MD Department of Orthopaeic Surgery, Washington University School of Meicine, 660 South Eucli, Campus Box 8233, St. Louis, MO aress: gelbermanr@wustl.eu Davi Samson, Esq Wolff an Samson PC, The Offices at Crystal Lake, One Bolan Drive, West Orange, NJ Sohail K. Mirza, MD, MPH Department of Orthopaeics, Dartmouth-Hitchcock Meical Center, One Meical Center Drive, Lebanon, NH John J. Callaghan, MD Department of Orthopaeic Surgery, University of Iowa Health Care, 200 Hawkins Drive, JPP, Iowa City, IA Vincent D. Pellegrini Jr., MD Department of Orthopaeics, University of Marylan School of Meicine, 22 South Greene Street, Suite S11B, Baltimore, MD aress: vpellegrini@umoa.umm.eu References 1. Leaf C. The law of unintene consequences. Fortune. 2005;152:250-2, 254, Campbell EG, Gruen RL, Mountfor J, Miller LG, Cleary PD, Blumenthal D. A national survey of physician-inustry relationships. N Engl J Me. 2007;356: Bekelman JE, Li Y, Gross CP. Scope an impact of financial conflicts of interest in biomeical research: a systematic review. JAMA. 2003;289: Campbell EG, Weissman JS, Ehringhaus S, Rao SR, Moy B, Feibelmann S, Gool SD. Institutional acaemic inustry relationships. JAMA. 2007; 298: Boy EA, Bero LA. Assessing faculty financial relationships with inustry: a case stuy. JAMA. 2000;284: McCrary SV, Anerson CB, Jakovljevic J, Khan T, McCullough LB, Wray NP, Broy BA. A national survey of policies on isclosure of conflicts of interest in biomeical research. N Engl J Me. 2000;343: Rothman DJ. 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